Extracts prepared from blood lymphocytes of normal subjects and patients with CLL were analyzed by high pressure liquid chromatography. A peak eluting after the nucleosides but before the nucleotides is present in a much higher concentration in CLL lymphocytes. Evidence to date indicates that the principal components in this peak are orotic acid with some admixture of dihydroorotic acid and orotidine. The research plan is as follows: 1) Definitive identification of the compounds is planned. 2) The reason for the accumulation will be determined by measuring the rate of pyrimidine biosynthesis, pyrophospho-ribosyl-phosphate, and enzyme levels in normal and CLL lymphocytes. Once the cause for the orotate accumulation is established, its effects on the immune response will be investigated and attempts made to overcome this block in CLL lymphocytes. This study will provide the reason for the orotate accumulation and its immunologic consequences. It may suggest how to correct or bypass the block in these immunodeficient cells.